DESCRIPTION, OVERALL (provided by applicant): The interdepartmental CURE: Digestive Diseases Research Core Center (CURE: DDRCC), funded continuously since 1989, is composed of 68 members and 26 associate members comprising a multidisciplinary group of physicians and basic scientists with strong independent peer-reviewed grant-supported programs in basic, translational and clinical research of the digestive system. Annual direct digestive diseases-related grant support for the research base is $16,858,584 including $6,089,729 from NIDDK. The current programs of this Research Base can be broadly divided in three major and interrelated complementary areas: A) Molecular and integrative mechanisms of gastrointestinal and pancreatic physiology and inflammation; B) Bidirectional brain-gut interactions and functional disorders of the digestive system; C) Mechanism of action of neuro-hormonal Gl signals: receptor regulation, signal transduction and control of normal and abnormal cell proliferation. The Biomedical Research Cores outlined in this proposal provide ready access to technologies and to clinical and biological materials that are essential to the programs of center members. These Cores offer access to modern cellular imaging to study signaling proteins and their functions, facilitate intestinal stem cell biology, provide animal models and techniques for studying integrative physiology and pathophysiology, molecular vectors to express a wide variety of proteins and access to a broad range of techniques and patients for clinical studies. The Administrative Core gives a wide range of administrative support for members and for center activities, including a comprehensive and multidisciplinary enrichment program. The Pilot and Feasibility Study program has provided a very successful mechanism for promoting the development of new programs and ideas in digestive diseases related research, primarily by young investigators. The CURE: DDRCC, enhanced by substantial direct institutional support, provides a forum, strategic vision and programmatic integration in which faculty members can advance the understanding of fundamental mechanisms relating to the function, disorders and diseases of the digestive system by making their combined efforts much greater than the sum of the parts.